Sitges M, Rodríguez R M
Depto. de Biología Celular, Instituto de Investigaciones Biomédicas, UNAM, México, DF.
Neurochem Res. 1998 Apr;23(4):477-85. doi: 10.1023/a:1022470215566.
The effects of external pH (pHout) variations on the Na+ and on the Ca2+ dependent fractions of the evoked amino acid neurotransmitter release were separately investigated, using GABA as a model transmitter. In [3H]GABA loaded mouse brain synaptosomes, the external acidification (pHout 6.0) markedly decreased the Na+ dependent fraction of [3H]GABA release evoked by veratridine (10 microM) in the absence of external Ca2+, as well as the Ca2+ dependent fraction of [3H]GABA release evoked by high (20 mM) K+ in the absence of external Na+. The depolarization-induced elevation of [Na(i)] (monitored in synaptosomes loaded with the Na+ indicator dye, SBFI) and the depolarization-induced elevation of [Ca(i)] (monitored in synaptosomes loaded with the Ca2+ indicator dye fura-2) were also markedly decreased at pHout 6. On the contrary, the external alkalinization (pHout 8) facilitated all the above responses. A slight increase of the baseline release of the [3H]GABA was observed when pHout was changed from 7.4 to 8. This effect was only observed in the presence of Ca2+. pHout changes from 7.4 to 6 or to 7 did not modify the baseline release of the transmitter. All the effects of pHout variations on [3H]GABA release were independent on the presence of HCO3-. It is concluded that external H+ regulate amino acid neurotransmitter release by their actions on presynaptic Na+ channels, as well as on presynaptic Ca2+ channels.
以γ-氨基丁酸（GABA）作为模型递质，分别研究了细胞外pH值（pHout）变化对诱发的氨基酸神经递质释放中Na⁺依赖性和Ca²⁺依赖性部分的影响。在装载了[³H]GABA的小鼠脑突触体中，细胞外酸化（pHout 6.0）显著降低了在无细胞外Ca²⁺时由藜芦碱（10 μM）诱发的[³H]GABA释放的Na⁺依赖性部分，以及在无细胞外Na⁺时由高钾（20 mM）诱发的[³H]GABA释放的Ca²⁺依赖性部分。在pHout为6时，去极化诱导的[Na(i)]升高（在用Na⁺指示剂染料SBFI装载的突触体中监测）和去极化诱导的[Ca(i)]升高（在用Ca²⁺指示剂染料fura - 2装载的突触体中监测）也显著降低。相反，细胞外碱化（pHout 8）促进了上述所有反应。当pHout从7.4变为8时，观察到[³H]GABA的基础释放略有增加。这种效应仅在有Ca²⁺存在时观察到。pHout从7.4变为6或7时，并未改变递质的基础释放。pHout变化对[³H]GABA释放的所有影响均与HCO₃⁻的存在无关。结论是细胞外H⁺通过作用于突触前Na⁺通道以及突触前Ca²⁺通道来调节氨基酸神经递质的释放。
